EMA Accepts MAA Filing of Eisai's Perampanel for the Treatment of Epilepsy

News provided by

Eisai

27 Jun, 2011, 23:59 BST

HATFIELD, England, June 27, 2011 /PRNewswire/ --

Eisai today announced that the European Medicines Agency (EMA) has accepted for review the Marketing Authorisation Application (MAA) for perampanel as a treatment for partial-onset seizures in patients with epilepsy. Perampanel is a first-in-class, highly selective non-competitive AMPA-type glutamate receptor antagonist.

Epilepsy is one of the most common neurological conditions in the world and an estimated 6 million people live with epilepsy in Europe.[1] The successful treatment of partial-onset seizures (the most common type of epilepsy) remains a challenge. Up to 30% of patients with partial-onset seizures do not achieve seizure freedom despite appropriate therapy with anti-epileptic drugs.[2]

"The acceptance of this application by the EMA is a positive step in the process towards bringing this important therapy to epilepsy patients with uncontrolled partial-onset seizures," commented, Professor Bernhard Steinhoff, Medical Director and Executive Chief Physician of the epilepsy clinic for adults, Kork Epilepsy Centre, Germany. "Uncontrolled seizures have a severe impact on patient quality of life and everyday function, so we look forward to the possibility of being able to offer epilepsy patients a new treatment option in the near future."

The efficacy, safety and tolerability of perampanel has been demonstrated by three Phase III global, randomized, double-blind, placebo-controlled, dose-escalation studies in 1,480 epilepsy patients. The primary and secondary endpoints were the same in all the studies: 50% responder rate, standard median percent seizure reduction, percentage reduction of complex partial plus secondarily generalized seizures, and evaluation for dose response.

Each of the studies showed consistent results in the efficacy and tolerability of perampanel in patients with partial-onset seizures.

Perampanel also has the benefit of once daily dosing, helping to reduce the potential pill-burden a person with epilepsy may experience.  

"As a research-based pharmaceutical company with a particular focus on epilepsy, we are committed to bringing innovative new epilepsy therapies to market that offer patients the opportunity for improved seizure control," said Lynn D. Kramer, M.D., FAAN, President, Eisai Neuroscience Product Creation Unit.  "Perampanel is an exciting new product that has the potential to address the strong unmet need in epilepsy patients and fits entirely within Eisai's human health care mission."

The development of perampanel is a good example of Eisai's human health care corporate mission, the company's commitment to innovative solutions in disease prevention, cure and care for the health and well being of people worldwide.  Eisai is committed to the therapeutic area of epilepsy and addressing the unmet medical needs of patients with epilepsy and their families.

Eiasi has also simultaneously submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for perampanel for adjunctive treatment of partial-onset seizures associated with epilepsy.

About Perampanel

Perampanel is a highly selective, non-competitive AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor antagonist that has demonstrated anti-seizure effects in Phase II and III studies. AMPA receptors, widely present in almost all excitatory neurons, transmit signals stimulated by the excitatory neurotransmitter glutamate within the brain and are believed to play a role in central nervous system diseases characterized by excess neuroexcitatory signalling including epilepsy, neurodegenerative disorders, movement disorders, pain and psychiatric disorders.

If approved, perampanel will be the first product in this class.

About the perampanel Phase III studies (Study 306, 305 and 304)

The clinical development plan for perampanel consisted of three global Phase III studies: Studies 306, 305 and 304 in which a total of 1,480 patients participated. The key goal of Study 306 was to identify the minimal effective dose and included four treatment arms (placebo, 2mg, 4mg, and 8mg). Studies 304 and 305 included three arms (placebo, 8mg, and 12mg) and were to evaluate a more extended dose range.

The studies were similar in design: global, randomized, double-blind, placebo-controlled, dose-escalation, parallel-group studies. The primary and secondary endpoints were the same in all the studies: percentage change in seizure frequency, 50% responder rate, percentage reduction of complex partial plus secondarily generalized seizures, and evaluation for dose response.

Study 306[3]

Study 306 showed that perampanel was well-tolerated and effective in reducing median seizure frequency and increasing responder rates. Specifically the results showed:

  • The results of the full ITT population showed: 2 mg = -13.6% (p=0.420), 4 mg = -23.3% (p=0.003), 8 mg = -30.8% (p<0.001). A significant change in median seizure frequency for the ITT population receiving 4 and 8 mg perampanel/day compared to placebo was: -28.6% for 4 mg (p=0.003) and -33.5% for 8 mg (p<0.001) versus -13.8% with placebo.
  • The results of the full ITT population showed: 2 mg = 20.6% (p=0.486), 4 mg = 28.5% (p=0.013), 8 mg = 34.9 (p=0.0003). Higher responder rates compared to placebo for the ITT population: 20.9% (p=ns), 28.6% (p=0.009), and 34.9% (p<0.001) in the 2, 4, and 8 mg perampanel/day groups, respectively, versus 17.6% with placebo.
  • The most frequent treatment-emergent adverse events were dizziness, headache and somnolence.

Study 305 - Europe, USA, South Africa, Israel, Russia, India, Australia

Full results of study 305 will be presented at the 29th International Epilepsy Congress in Rome, 28th August -1st September, 2011.

Study 304[4] - USA, Canada and South America

Study 304 showed consistent results in the efficacy and tolerability of perampanel given as a treatment for patients with partial-onset seizures. Specifically:

  • A full intention-to-treat analysis indicated that the placebo group, the 8-mg group, and the 12-mg group had a 21.0%, 26.3%, and 34.5% reduced seizure frequency, respectively.
  • The 50% responder rates in the placebo group, 8-mg group, and 12-mg group were 23.4%, 37.6%, and 36.1%, respectively.
  • The most common side effects were dizziness, somnolence, irritability, headache, falls, and ataxia.

About Epilepsy

Epilepsy is one of the most common neurological conditions in the world, affecting approximately 8 in 1,000 people in Europe[5]. There is an estimated 6 million people living with epilepsy in Europe[1] and estimated 50 million people worldwide.[6]

Epilepsy is characterised by abnormal firing of impulses from nerve cells in the brain causing seizures. Depending on the seizure type, seizures may be limited to one part of the body, or may be generalised to involve the whole body.

In partial-onset seizures, these bursts of electrical activity are initially focused in specific areas of the brain,[7] but may become generalised;[7] the symptoms vary according to the affected areas.[8]

Patients may also experience abnormal sensations, altered behaviour or altered consciousness. Epilepsy is a disorder with many possible causes. Often the cause of epilepsy is unknown. However, anything that disturbs the normal pattern of neuron activity - from illness to brain damage to tumours, can lead to seizures.[9]

Treatment of partial-onset seizures, the most common type of epilepsy, presents a constant challenge - Up to 30% of patients with partial seizures do not achieve remission despite appropriate therapy with anti-epileptic drugs.[2]

Furthermore, central nervous system related adverse events, such as lightheadedness (dizziness), somnolence (sleepiness), cognitive slowing (attention and memory deficits) and aggression, are highly prevalent with existing anti-epileptic agents.[10,11,12] Hence, there is a need for new anti-epileptic agents that offer effective reduction in seizure frequency combined with a favourable safety profile.

About Eisai Europe in Epilepsy

Eisai is committed to developing and delivering highly beneficial new treatments to help improve the lives of people with epilepsy. The development of anti-epileptic drugs (AEDs) is a major strategic area for Eisai in the European market.

In Europe, Eisai currently has three marketed treatments including:

  • Zonegran® (zonisamide) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalization.
  • Zebinix® (eslicarbazepine acetate) as adjunctive therapy in adult patients with partial-onset seizures, with or without secondary generalization. (Zebinix is under license from BIAL)
  • Inovelon® (rufinamide) for adjunctive treatment, 4 years and older of seizures associated with Lennox-Gastaut Syndrome.

About Eisai

Eisai is one of the world's leading research-based pharmaceutical companies that has defined its corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call human health care (hhc). Eisai concentrates its research activities in three key areas

  • Neuroscience including: Epilepsy, Alzheimer's disease, multiple sclerosis, neuropathic pain and depression.
  • Oncology including: anticancer therapies; tumour regression, tumour suppression, antibodies, etc and supportive cancer therapies; pain relief and nausea.
  • Vascular/Immunological Reaction including: acute coronary syndrome, atherothrombotic disease, sepsis, rheumatoid arthritis, psoriasis and Crohn's disease.

With operations in the U.S., Asia, Europe and its domestic home market of Japan, Eisai employs more than 11,000 people worldwide.

In Europe, Eisai undertakes sales and marketing operations in over 20 markets, including the United Kingdom, France, Germany, Italy, Spain, Switzerland, Sweden, Ireland, Austria, Denmark, Finland, Norway, Portugal, Iceland, Czech Republic, Hungary, Slovakia, the Netherlands, Belgium and Luxembourg.

For further information please visit our web site http://www.eisai.co.jp

References

1.  ILAE/IBE/WHO, Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe 2010. Available from; http://www.ilae-epilepsy.org/Visitors/Documents/EUROReport160510.pdf  (Accessed June 2011)

2. Kwan P, Brodie MJ Early identification of refractory epilepsy.  New England Journal of Medicine 2000; 342: 314-9.

3. G. L. Krauss, J. M. Serratosa, V. E. Villanueva, M. Endziniene, Z. Hong, J. French, H. Yang, D. Squillacote, J. Zhu, A. Laurenza, American Epilepsy Society Efficacy and safety of perampanel, an AMPA receptor antagonist, as an adjunctive therapy in a Phase III study of patients with refractory partial-onset seizures. Available at URL http://www.aesnet.org/go/publications/aes-abstracts/abstract-search/mode/display/st/perampanel/sy/2010/sb/All/id/13437  (Accessed June 2011)

4. Perampanel Reduces Treatment-Resistant, Partial-Onset Seizures. Neurology Reviews 2011;19(6):1,26-29.  

5. Pugliatti M et al. Estimating the cost of epilepsy in Europe: A review with economic modeling. Epilepsia 2007: 48(12) 2224 - 2233

6. Epilepsy Society UK: http://www.epilepsysociety.org.uk/AboutEpilepsy/Whatisepilepsy/Epilepsy-didyouknow  (Accessed June 2011)

7. Epilepsy Action. Describing Seizure Types. Avaiable at URL http://www.epilepsy.org.uk/info/seizures/ataglance  (Accessed June 2011)

8. NHS Choices. Symptoms of Epilepsy. Available at URL http://www.nhs.uk/Conditions/Epilepsy/Pages/Symptoms.aspx  (Accessed June 2011)

9. Epilepsy Research UK. What is Epilepsy? Fact sheet. Avaiable from URL: http://www.epilepsyresearch.org.uk/about_us/leaflets/lflt1.htm  (accessed March 16 2011)

10. Topamax Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/6768 (Accessed June 2011)

11. Carbamazepine Summary of Product Characteristics. Available at: http://www.medicines.org.uk/EMC/medicine/1328/SPC/Tegretol+Chewtabs+100mg%2c+200mg%2c+Tegretol+Tablets+100mg%2c+200mg%2c+400mg/ (Accessed June 2011)

12. Oxcarbazepine Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/2673/SPC/#INDICATIONS (Accessed June 2011)

SOURCE Eisai